Proposed is the acquisition of a high resolution scanning electron microscope which will be equipped with a multifunctional detector for secondary and backscatter electron imaging and which will be configured to allow signal mixing, inversion and detail enhancement by mixing the derivative of the video signal with the unprocessed signal. These features, when combined with the capacity for low voltage operation, will meet pressing needs throughout the institution as exemplified in the six NIH funded core research projects. The core projects involve investigators from five academic departments, and the studies encompass four distinct biomedical areas including: (1) retinal regeneration following injury, (2) pathogenesis of atherosclerosis, (3) cellular and biochemical events in thrombosis and thrombolysis, (4) sensory (hearing) loss due to perilymphatic fistulas. At the cellular and sub-cellular levels the projects address questions of endothelial turnover, neuronal migration and differentiation, the role of the extracellular matrix in cell regulation, and the distribution of surface receptors during platelet activation and macrophage foam cell formation. These diverse questions will draw upon different features of the scanning electron microscope with the precision eucentric tilt microstage being used for spatial (3-dimensional) questions related to fibrin/platelet interaction during thrombogenesis and the organization of extracellular matrix components at the surface of endothelial and smooth muscle cells. The backscatter detector will be used in conjunction with autoradiography and gold colloid chemistry to determine lipoprotein receptor distribution and cell damage and turnover in cardiovascular disease; it will also be used in studies describing cell surface receptors for extracellular matrix components and for components of the multienzyme procoagulant complex on platelets. Four of the projects will rely heavily upon the capacity for signal integration in experiments designed to co-localize two or more receptors or ligands on cell and tissue surfaces. The instrument will be incorporated into the institutional electron microscopy laboratory, which is maintained in the Department of Pathology. Within the context of an institutional facility, the instrument will be available to numerous investigators from throughout the University.